Social support following a stressful life event can attenuate stress response systems, such as the activation of the hypothalamic-pituitary-adrenal (HPA) axis, and reduce the odds of psychological distress or a panic disorder;this is known as social buffering. This is particularly true when support is derived from a social partner (e.g., spouse). However, biological factors that are involved with social support and their influence on the HPA axis following a stressful event are understudied due to the lack of appropriate animal models that can examine support from a social partner. The pair-bonding behavior in monogamous prairie voles (Microtus ochrogaster) is well characterized and represents a unique model system to study brain-behavior relationships. This proposal will use prairie voles as a model system to identify neuroendocrine mechanisms of social support following a stressful experience, particularly the mediating effects of the neuropeptide oxytocin (OT). The prairie vole is a highly social, monogamous rodent that breeds readily in captivity and forms a long-term social preference for their partner, a traditional characteristic of pair-bond formation. Like humans, contact with a social partner can attenuate the behavioral and HPA axis response to a stressful event. In addition, positive social interactions promote brain OT release in prairie voles, and OT release in the hypothalamic paraventricular nucleus (PVN) - which also contains corticotropin-releasing hormone neurons that project to the pituitary to control adrenocorticotropic hormone secretion and subsequent adrenal glucocorticoid release - attenuates stress reactivity. Therefore, prairie voles may serve as a unique model system to study the anxiolytic effects of interaction with a social partner following a stressful event and the potentially mediating role of OT. By using prairie voles in a social buffering stress paradigm, the results from this proposal should: (1) characterize the anxiolytic effects of interactions with a social partner and OT following a stressful event, (2) identify the role that OT has in the social buffering of the biobehavioral stress response, and (3) present neuronal phenotypes in several brain regions that are influenced by social interaction-induced OT release following a stressful experience. This research program represents several steps in examining the neurobiology mechanism underlying the social buffering effect in prairie voles. PUBLIC HEALTH RELEVANCE: Social support following a stressful life event can attenuate stress responses, but unfortunately, individuals at the greatest risk for stress-induced mental and physical health disturbances may also lack the appropriate level and source of social support. Here, I propose to use the socially monogamous prairie vole (Microtus ochrogaster) as a model system to investigate the neuroendocrine mechanisms mediating social support following a stressful life event, given the immense impact stress can have on an individual's well being. A better understanding of the neuroendocrine mechanisms may direct clinicians to potential therapeutic treatments - targeting the central neurotransmitter system in the development of anxiolytics - for patients at risk of experiencing stressful life events and subsequent stress-related psychological disorders, particularly those with inadequate social support.